US2025115582A1PendingUtilityA1
Molecular glue degraders and methods of using the same
Assignee: MONTE ROSA THERAPEUTICS INCPriority: Jun 16, 2022Filed: Dec 16, 2024Published: Apr 10, 2025
Est. expiryJun 16, 2042(~15.9 yrs left)· nominal 20-yr term from priority
C07D 417/14C07D 413/14C07D 401/12C07D 401/04C07D 211/42A61K 45/06A61K 31/506A61K 31/497A61K 31/4545A61K 31/454A61K 31/451A61P 35/00C07D 401/14
60
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Claims
Abstract
Described herein, in part, are compounds that mediate the degradation of casein kinase 1α (CK1α), and are therefore useful in the treatment of various disorders, such as cancer.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of Formula (I):
or a pharmaceutically acceptable salt thereof,
wherein:
R 1 is selected from the group consisting of phenyl, heteroaryl, cycloalkyl, and heterocyclyl, wherein each of phenyl, heteroaryl, cycloalkyl, and heterocyclyl is optionally substituted with one or more occurrences of R A ;
each of R 2 , R 2b , and R 2c is independently selected from the group consisting of H, C 1-3 alkyl, and C 1-3 alkoxy;
each occurrence of R A is independently selected from the group consisting of oxo, halogen, C 1-6 alkyl, C 1-3 alkoxy, cyano, cycloalkyl, heteroaryl, and phenyl, wherein each of C 1-6 alkyl, cycloalkyl, heteroaryl, and phenyl is optionally substituted with one or more occurrences of R B , or one or more groups of two occurrences of R A , together with the carbon to which they are attached, form oxo;
each occurrence of R B is independently selected from the group consisting of halogen, C 1-6 alkyl, and C 1-6 alkoxy;
R 3 is hydrogen, C 1-3 alkyl, or C 1-3 haloalkyl,
or R 1 and R 3 can, together with the atoms to which they are attached, form a 9-10 membered heterocyclyl optionally substituted by one or more oxo; and
n is 0 or 1.
2 . The compound of claim 1 , wherein R 1 is 5 or 6-membered heteroaryl optionally substituted with one or more occurrences of R A .
3 . The compound of claim 1 , wherein R 1 is phenyl optionally substituted with one or more occurrences of R A .
4 . The compound of claim 1 or 2 , wherein R 1 is pyridinyl optionally substituted with one or more occurrences of R A .
5 . The compound of claim 1 or 2 , wherein R 1 is thiazolyl, imidazolyl or oxazolyl optionally substituted with one or more occurrences of R A .
6 . The compound of claim 1 or 2 , wherein R 1 is 5 or 6-membered heteroaryl substituted with one or more occurrences of R A .
7 . The compound of claim 1 or 3 , wherein R 1 is phenyl substituted with one or more occurrences of R A .
8 . The compound of claim 1, 2, or 6 , wherein R 1 is 5 or 6-membered heteroaryl substituted with one or two occurrences of R A .
9 . The compound of claim 1, 2, 6, or 8 , wherein R 1 is pyridinyl substituted with one or two occurrences of R A .
10 . The compound of claim 1, 3, or 7 , wherein R 1 is phenyl substituted with one or two occurrences of R A .
11 . The compound of claim 1, 2, 6, or 8 , wherein R 1 is 5 or 6-membered heteroaryl substituted with one or two occurrences of halogen.
12 . The compound of claim 1, 2, 6, 8, or 9 , wherein R 1 is pyridinyl substituted with one or two occurrences of halogen.
13 . The compound of claim 1, 3, 7, or 10 , wherein R 1 is phenyl substituted with one or two occurrences of halogen.
14 . The compound of claim 1, 2, 6, or 8 , wherein R 1 is 5 or 6-membered heteroaryl substituted with methyl, wherein methyl is optionally substituted with one more occurrences of halogen.
15 . The compound of claim 1, 2, 6, 8, or 14 wherein R 1 is pyridinyl substituted with methyl, wherein methyl is optionally substituted with one more occurrences of halogen.
16 . The compound of claim 1, 3, 7, or 10 , wherein R 1 is phenyl substituted with methyl, wherein methyl is optionally substituted with one more occurrences of halogen.
17 . The compound of claim 1 , wherein R 1 is 8-10 membered bicyclic heterocyclyl optionally substituted by one or more oxo.
18 . The compound of claim 17 , wherein R 1 is indolinyl optionally substituted by one or more oxo.
19 . The compound of claim 1 , wherein R 1 is 9-10 membered bicyclic cycloalkyl.
20 . The compound of claim 1 , wherein R 1 is 5-6 membered monocyclic heterocyclyl optionally substituted by one or more C 1-6 alkyl, wherein the alkyl is optionally substituted by one or more halogen.
21 . The compound of any one of claims 1-20 , wherein R 2a , R 2b , and R 2c are H.
22 . The compound of any one of claims 1-20 , wherein each of R 2a , R 2b , and R 2c is independently selected from the group consisting of C 1-3 alkyl and C 1-3 alkoxy.
23 . The compound of claim 22 , wherein each of R 2a , R 2b , and R 2c is independently selected from the group consisting of methyl, ethyl, and methoxy.
24 . The compound of any one of claims 1-23 , wherein each occurrence of R A is independently selected from the group consisting of halogen, C 1-3 alkyl, and cyano, wherein C 1-3 alkyl is optionally substituted with one or more occurrences of halogen.
25 . The compound of any one of claims 1-24 , wherein each occurrence of R A is independently selected from the group consisting of F, Cl, methyl, ethyl, isopropyl, and cyano, wherein each of methyl, ethyl, and isopropyl is optionally substituted with one or more occurrences of F.
26 . The compound of any one of claims 1-25 , wherein each occurrence of R A is independently selected from the group consisting of C 1 and methyl.
27 . The compound of any one of claims 1-23 , wherein each occurrence of R A is independently selected from the group consisting of phenyl and heteroaryl.
28 . The compound of any one of claims 1-27 , wherein each occurrence of R B is independently selected from the group consisting of F, Cl, methyl, ethyl, and cyano, wherein each of methyl and ethyl is optionally substituted with one or more occurrences of F.
29 . The compound of any one of claims 1-28 , wherein R t is selected from the group consisting of:
30 . The compound of claim 29 , wherein R 1 is selected from the group consisting of:
31 . The compound of claim 27 , wherein R 1 is selected from the group consisting of:
32 . The compound of any one of claims 1-31 , n is 1.
33 . The compound of any one of claims 1-31 , n is 0.
34 . A compound selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
35 . A pharmaceutical composition comprising the compound of any one of claims 1-34 , or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
36 . A method of degrading CK1a in a subject suffering from cancer, comprising administering to the subject an effective amount of the compound of any one of claims 1-34 , or pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 35 .
37 . A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of any one of claims 1-34 , or pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 35 .
38 . A method of treating a solid tumor in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of any one of claims 1-34 , or pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 35 .
39 . A method of treating a liquid tumor in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of any one of claims 1-34 , or pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 35 .
40 . The method of any one of claims 36-39 , further comprising administering to the subject an additional therapeutic agent.Join the waitlist — get patent alerts
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